GB2061278A - Total Synthesis of A-nor and A- dinor Steroids - Google Patents
Total Synthesis of A-nor and A- dinor Steroids Download PDFInfo
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- GB2061278A GB2061278A GB8026582A GB8026582A GB2061278A GB 2061278 A GB2061278 A GB 2061278A GB 8026582 A GB8026582 A GB 8026582A GB 8026582 A GB8026582 A GB 8026582A GB 2061278 A GB2061278 A GB 2061278A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J63/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton has been modified by expansion of only one ring by one or two atoms
- C07J63/008—Expansion of ring D by one atom, e.g. D homo steroids
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
- C07C49/385—Saturated compounds containing a keto group being part of a ring
- C07C49/417—Saturated compounds containing a keto group being part of a ring polycyclic
- C07C49/423—Saturated compounds containing a keto group being part of a ring polycyclic a keto group being part of a condensed ring system
- C07C49/453—Saturated compounds containing a keto group being part of a ring polycyclic a keto group being part of a condensed ring system having three rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/10—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings
- C07D317/14—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D317/26—Radicals substituted by doubly bound oxygen or sulfur atoms or by two such atoms singly bound to the same carbon atom
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/10—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings
- C07D317/14—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D317/30—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J61/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton has been modified by contraction of only one ring by one or two atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2603/00—Systems containing at least three condensed rings
- C07C2603/02—Ortho- or ortho- and peri-condensed systems
- C07C2603/04—Ortho- or ortho- and peri-condensed systems containing three rings
- C07C2603/06—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members
- C07C2603/10—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members containing five-membered rings
- C07C2603/12—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members containing five-membered rings only one five-membered ring
- C07C2603/16—Benz[e]indenes; Hydrogenated benz[e]indenes
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Abstract
Compounds of formula <IMAGE> (wherein n is 0 or 1, R is Me or Et, R1 is H, A or COA where A is alkyl, cycloalkyl or aryl, and R2 is H or Me) are prepared from sulphones of formula <IMAGE> by a multistep synthesis which commences by reacting the sulphone with methyl 6,6-ethylenedioxy-3- oxoheptanoate or methyl 5,5- ethylenedioxy-3-oxohexanoate. When R2=H and n=1 the intermediate from which the tetracyclic ring system is generated is of formula <IMAGE>
Description
SPECIFICATION
Process for Synthesizing A-nor and A-nor-l 8-homo-steroids
The present invention is related to a process for synthesizing A-nor and A-nor-l 8-homo-steroids.
The invention is particularly concerned with providing a total synthesis for the compounds called
Dinordrin and 1 8-homo-Dinordrin although the preparation of other related compounds will also be evident.
Dinordrin (la) and 18-homo-Dinordrin (ib) in the form oftheirpropionate esters, may be structurally illustrated as follows:
These compounds have been reported to have unusual fertility inhibitor properties. For example,
Dinordrin appears to be about ten times more potent than Anordrin (the dipropionate of 2a,1 7a- diethynyl-A-nor-5-androstane-2p,1 7p-diol). See P. Crabbe, H. Fillion, Y. Letourneux, E. Diczfalusy, A.
R. Aedo, J. W. Goldzieher, A. A. Shaikh, and V. D. Castracane, Steroids, 1979, 33, 85; P. Crabbe, D.
Andre and H. Fillion, Tetrahedron Letters, 1979, 893.
Prior procedures for preparing 1 a and 1 b and generally similar products, including Anordrin, are inconveniently lengthy and low yielding and there is a real need for a versatile, short, total synthetic scheme for preparing these products. The principal object of the present invention is to provide such a process. A more specific object is to provide a relatively short synthetic route which affords the desired products in a convenient manner and in good yield. Other objects will also be hereinafter evident.
According to one aspect of the invention a process for preparing A-nor and A-nor-l 8-homosteroids of the formula:
wherein n=1 or 0, R is methyl or ethyl; R is hydrogen or
wherein A is lower alkyl, cyclo-alkyl or aryl; and R2 is hydrogen or methyl comprises
(a) reacting an optically active trans-fused bicyclic diketo-sulfone of the formula
with a 6-(1 ,3-dioxolan-2-yl)-3-oxoheptanoic acid methyl ester or with a 5-(1 ,3-dioxolan-2
yl)-3-oxohexanoic acid methyl ester to obtain a triketo derivative; (b) hydrolyzing, cyclizing and decarboxylating the product of step (a) to obtain an enone; (c) catalytically hydrogenating said enone to obtain a dione; (d) acid hydrolyzing to obtain a trione; (e) cyclizing the product of step (d) to obtain a mixture of isomeric enones;;
(f) subjecting said mixture to Birch reduction and oxidation to obtain the corresponding saturated
2,1 7-dione with the A:B trans stereochemistry;
(g) ethynylating the product of step (f) to obtain a mixture of 2a- and 2p-isomers; and
(h) separating the isomers by chromatography.
According to a second aspect of the invention, a process for preparing A-nor and A-nor-18- homo-steroids of the formula:
wherein n=1 or 0, R is methyl or ethyl; R1 is hydrogen and R2 is hydrogen or methyl comprises
(a) reacting an optically active trans-fused bicyclic diketosulphone of the formula::
with a 6-(1 ,3-dioxolan-2-yl)-3-oxoheptanoic acid methyl ester or with a 5-(1 ,3-dioxolan-2
yl)-3-oxohexanoic acid methyl ester to obtain a triketo derivative;
(b) hydrolyzing, cyclizing and decarboxylating the product of step (a) to obtain an enone;
(c) catalytically hydrogenating said enone to obtain a dione;
(d) acid hydrolyzing to obtain a trione;
(e) cyclizing the product of step (d) to obtain a mixture of isomeric enones;
(f) subjecting said mixture to Birch reduction and oxidation to obtain the corresponding saturated
2,1 7-dione with the A:B trans stereochemistry;
(g) ethynylating the product of step (f) to obtain a mixture of 2ar- and 2p-isomers; and
(h) separating the isomers by chromatography.
According to a third aspect of the invention, a process for preparing A-nor and A-nor-1 8-homosteroids of the formula:
wherein n=1 or 0, R is methyl or ethyl; R1 is
wherein A is lower alkyl, cyclo-alkyl or aryl; and R2 is hydrogen or methyl comprises esterifying the 2a isomer product of the second aspect of the invention.
According to a fourth aspect of the invention, a process for preparing A-nor and A-nor-1 8-homosteroids of the formula:
wherein n=1 or 0, R is methyl or ethyl; R1 is lower alkyl, cyclo-alkyl or aryl; and R2 is hydrogen or methyl comprises esterifying the 2a isomer product of the second aspect of the invention.
Broadly speaking, the products which may be prepared according to the present process include those of the Formula I:
wherein n=1 or 0, R is methyl or ethyl; R1 is hydrogen or
wherein A is preferably lower alkyl; cycloalkyl or aryl; and R2 is hydrogen or methyl. It will be appreciated that Dinordrin is represented by Formula I when n=1, fl is methyl, R10 is a propionate and
R2 is hydrogen while, in 1 8-homo-Dinordrin, R is ethyl R1O is a propionate and R2 is hydrogen.
Anordrin is represented by Formula I when n=1, R and R2 are both methyl and R, is
It will be appreciated that the products are normally prepared as mixtures of the 2a,1 7a-ethynyl and 2,B,1 7,B-ethynyl isomers. Then 2a,1 7a isomer is preferred for biological use.
The reaction scheme involved in the present process is represented below.
The process of the invention involves the use of an approach described by Schering A.G. (see (a)
G. Sauer, U. Eder, G. Haffer, G. Neef, and R. Wiechert,Agnew. Chem. Int. Ed. Engl., 14, 417 (1975); (b)
R. Wiechert,Agnew. Chem. Int. Ed. Engl., 16, 506 (1977) and references therein). There is, however, no indication in the Schering disclosures of the possibility of preparing A-nor steroids using this approach.
The starting material for the synthesis of Dinordrin is the known optically active trans-fused bicyclic diketo-sulfone (1) described in the abovementioned Schering A.G. publications. The crystalline dione (1) is reacted in a non-polar solvent with the anion prepared from 6-(1,3-dioxolon-2-yl)-3- oxoheptanoic acid methyl ester (2), in the presence of sodium or potassium hydride. A triketoderivative (3) is obtained and this is immediately hydrolized, cyclized and decarboxylated with base, to afford the enone (4) in high yield.
Catalytic hydrogenation of the conjugated ketone (4) gives the dione (5). Acid hydrolysis liberates the cycloethylene ketal, thus providing the crystalline trione (6)..
Cyclization of the tricyclic intermediate (6) in methanol solution in the presence of a base gives a mixture of isomeric enones (7) and (8). This mixture can either be separated or immediately submitted to a Birch reduction, followed by oxidation with pyridinium chlorochromate, thus providing the corresponding saturated, 2,17-dione (9). This material is shown to be identical by usual criteria (m.p.,
I.R., N.M.R., etc.) with an authentic sample of the dinordione (9), see: P. Crabbe, H. Fillion, Y.
Letourneux, E. Diczfalusy, A. R. Aedo, J. W. Goldzieher, A. A. Shaikh, and V. D. Castracane, Steroids, 33, 85 (1979). This confirms the correct configuration at all asymmetric centres, in particular the A:B trans stereochemistry, i.e. the cyclization process and the Birch reduction of both isomers (7) and (8) are completely stereoselective.
Treatment of the diketo-steroid (9) with an excess of lithium acetylide-ethylenediamine complex under known conditions, furnishes a mixture of 2a- and 2p-isomers, of which the desired 2ar-ethynyl steroid (10) may be separated by chromatography. Further esterification of the diol may be performed under known conditions.
The same reaction sequence may be applied to the known optically active 7a-p-ethyl-6H-7,7a- dihydroindane-1 ,5-dione to give the corresponding 18-homo dinor-steroid.
In addition the same synthetic route may also be applied to the synthesis of A-donor-steroids (i.e.
n in Formula I is O so that ring A is a four-member ring) using 5-(1 ,3-dioxolan-2-yl)-3-oxohexanoic acid methyl ester.
The invention is illustrated by the following example:
Example (a) 5-(1 ,3-Dioxolan-2-yl)-2-hexanone
22.8 g (0.2 Mol) Hexanedione-2,5, 12.4 g (0.2 Mol) ethylene glycol, and 0.5 g ptoluenesulphonic acid were refluxed for 1 8 hours in toluene on a Dean-Stark apparatus. Then the solution was washed twice with NaHCO3-solution, dried over K2C03 and concentrated in vacuo. The remaining oil was distilled over a 20 cm-Vigreux column. The middle fractions were redistilled to give the monoketal as a colourless liquid, b.p. 1 00--1 03 0/1 5 mm.
Alternatively the monoketal may also be prepared as follows:
A solution of 2,5-hexadione (23.4 ml, 0.2 mole) and ethyleneglycol (45 ml, 0.8 mol) in toluene (125 ml) was stirred in an ice bath for 1 5 min. After this time concentrated sulfuric acid (5 ml, 0.09 mole) was added and stirring was continued for 30 min. The lower layer containing mainly ethyleneglycol was separated and extracted with toluene twice. The combined organic layers were washed with a sodium bicarbonate solution (water and NaCI saturated solution). Toluene was evaporated and the remaining viscous liquid containing the starting material contained the mono and di-ketals. These were separated by vacuum distillation, affording the expected monoketal.
NMR (CDCl3): 1.30 (s, 3H); 2.10 (s, 3H); 1.65-2.65 (m, 4H; 3.85 p.p.m. (s, 4H)
IR: 1718 cm-l (b) 6-( 1 ,3-Dioxolan-2-yl)-3-oxoheptanoic Acid Methyl Ester
4.32 g Sodium hydride (50% in oil) were washed with pentane, dried and suspended in 30 ml of dry ether. At reflux temperature were added 5.40 g dimethyl carbonate (60 mMol) and then a solution of 4.74 g monoketal (30 mMol) in 20 ml of dry ether. After 4 hours the gas evolution was finished. The mixture was hydrolysed with 5 ml of ethanol, poured on a solution of 7 ml of acetic acid in 100 ml of water, neutralized with NaHCO3 and extracted with ether. The aqueous layer was extracted two more times with ether.The extracts were dried over K2CO3 and evaporated. The residue was distilled in vacuo, to give the ester as an oil.
NMR (CDCl3): 1.30 (s, 3H); 1.60-2.70 (m, 4H); 3.40 (s, 2H); 3.62 (s, 3H); 3.85 p.p.m. (s, 4H)
IR: 1750, 1718 cm-l
240 mg Sodium hydride (50% in oil, 5 mMol) were suspended in 20 ml of dry toluene. With stirring a solution of 640 mg (2 mMol) of crystalline sulfone (1) (m.p. 92--940; [a]+l 790) and 550 mg (2.5 mMol) ketal ester (2) in 20 ml of toluene was added over a period of 1 5 min. After 2 hours the solvent was removed in vacuo. The alkylation product was not isolated, but hydrolysed, cyclized and decarboxylated to give the unsaturated ketone (4).
The residue was dissolved in 20 ml of methanol and a solution of 0.5 g NaOH in 5 ml of water was added. After 10 hours, methanol was evaporated in vacuo and the aqueous solution was extracted with ether to remove paraffin (from NaH). The aqueous layer was acidified with acetic acid and extracted 3 times with methylene chloride. The extracts were dried over MgSO4 and evaporated in vacuo. The residue was refluxed in 30 ml of toluene for 30 min. Then the solvent was removed and the residue purified by chromatography (20 g SiO2, toluene/ethyl-acetate 4:1), affording the enone (4) as a colourless oil.
506 mg (1.6 mMol) of Enone (4) were dissolved in 50 ml of ethanol and 0.5 ml of triethylamine.
50 mg of Pd on charcoal (5%) were added and the mixture was stirred at room temperature for 5 hours. The catalyst was filtered off, solvent evaporated and the residue dissolved in 30 ml of acetone and 2 ml of 1 n HCI. After 30 min. the mixture was neutralized with NaHCO3, acetone was removed in vacuo; the aqueous solution was extracted 4 times with CH2CI2, the extracts dried over MgSO4 and evaporated. The residue was recrystallized from hexane/ether, providing the triketone (6), m.p. 133-134 , [α]D+129 ; NMR (CDCl3): 0.94 (s, 3H); 1.00-3.20, m; 2.20 p.p.m. (s)
IR (Nujol: 1742, 1705 cm-1
MS (70 eV): 274 (M-2), 258,233,220, 219 (100%), 177, 163.
276 mg (1 mMol) Trione (6) were refluxed for 10 hours in a solution of 1.7 g KOH in 30 mol of methanol. After evaporation of the solvent, water was added, acidified with acetic acid, neutralized with NaHCO3 and extracted three times with CH2CI2. The extracts were dried over K2CO3 and the solvent removed in vacuo. The residue crystallized from ether/hexane, to give a crystalline material, m.p. 135138 , mixture (1:1) of (7) and (8).
The pure A1,10-isomer (8) was obtained by recrystallization from hexane: m.p. 182-184 ; [ai+5l 0; U.V.max229 nm (e 13,000).
NMR (CDC13): 0.88 (s, 3H); 0.92 (s, 3H); 0.65-3.00 (m, 1 8H); 5.67 p.p.m. (s, 1 H) IR (Nujol): 1740, 1702 cm-l MS (70 eV): 259 (M+ 1); 258 (M+,100%); 240, 214, 202, 187, 174, 173, 160, 159, 149, 146, 145,134,132,131,119, 117,108,107,106, 105,97,96,95,94,93,91,81,79,77,67, 66,65,55,53,51.
50 mg (0.19 mMol) of the enone isomer mixture in 2 ml of dry ether were added to a solution of 100 mg of lithium in 20 ml of liquid ammonia. After 30 min., 1 g of ammonium chloride was added and the ammonia was allowed to evaporate. The residue was dissolved in water and extracted four times with methylene chloride. The extracts were dried over MgSO4 and stirred overnight with 0.5 g of
Pyridinium chlorochromate. It was hydrolyzed with potassium carbonate solution, separated, washed with 1 n HCI, dried over MgSO4 and evaporated. The resulting oil was purified by chromatography on 2 g of silica gel (Toluene/ethyl acetate 9:1), to furnish a colourless oil, which crystallized on standing.
M.p. (from hexane) 148151 . Recrystallization gave the pure sample of (9): m.p. 158--1600; [D+2620 IR (Nujol): 1 738 cm-l (identical with the spectrum of an authentic sample).
(g)
A current of dry acetylene was passed for 30 minutes through a solution maintained at 0 to 5 C, of 250 mg of the dione 9 of step (f) dissolved in 5 ml anhydrous dimethylsulfoxide (DMSO) to which 272 mg of lithium acetylide-ethylene diamine complex had been added. The reaction mixture was allowed to stand overnight at room temperature after which it was mixed with water. The reaction product comprising about a 3:2 mixture of isomeric 2-ethynyl derivatives was recovered and, after chromatography, the desired 2a,1 7adiethynyl-2,1 7-dihydroxy-A-nor-5a-estrane (10) was obtained, separated from the 2isomer (11). The separation was accomplished by thin layer chromatography using a 7 to 3 cyclohexane-ethyl acetate mixture as a solvent system.
The corresponding diesters, e.g. diacetates, dipropionates, divalerates, dibutyrates, dibenzoates, dienanthates, diundecanoates and the like may be prepared from the diol (10) by conventional esterification techniques. For example, the diol (about 700 mg) may be dissolved in about 3-5 ml of anhydrous pyridine with the addition of acid anhydride. The reaction mixture is then heated on an oil bath (11 1 1 50C) overnight after which methanol is added to remove excess anhydride. The reaction mixture is cooled and the diester extracted, washed and dried, solvent being removed by vacuum. The pure diester isomers may be obtained by chromatography or the diester may be prepared by esterification of the separated hydroxy isomer.For example, esterification with propionic anhydride of the 2p-hydroxyl isomer (m.p. 1450; [a]60) gives Dinordrin in the optically active form.
The diesters may also be prepared by reacting the diols with the appropriate acid chloride in inert solvent under mild reaction conditions.
Diethers may also be prepared by, for example, reacting the diol with dihydropyran in the presence of an acid such as p-toluene sulfonic acid. Monoethers may also be prepared in conventional fashion.
It is to be noted that, while the foregoing example is concerned with the preparation of 2a,1 7a- diethynyl-2,B,17,B-dihydroxy-A-nor-5a-estrane (Dinordrin), the corresponding 18-homo product may be prepared in similar fashion using the known methylene sulfone 7-p-ethyl-6H-7,7a-dihydroindane- 1,5-dione as starting material.
The sulfone starting material used in the example was prepared by treatment of optically active (+) 7-/3-methyl-6H-7,7a-dihydroindane-1,5-dione with paraformaldehyde and benzenesulflnic acid in triethanolamine, and acetic acid, followed by catalytic hydrogenation in the presence of palladium on
Charcoal (See again G. Sauer, U. Eder, G. Haffer, G. Neef, and R. Wiechert,Agnewchern. Intern. Ed., 1975, 14, 417). The sulfone was obtained in crystalline form (m.p. 92--940; []D+ 790) The corresponding ethyl starting material may be obtained in the same way.
It will be recognized that the procedure described above is short, flexible, and easy to perform, thus constituting a useful synthetic approach to the indicated class of biologically important A-nor steroids. It is noteworthy that the cyclization reaction of the intermediates (3), followed by the catalytic reduction of the enones (4), condensation and Birch reduction of the cyclopentenones (7) and (8) afforded the dione (9) with the correct stereochemistry at all asymmetric centers, thus showing the total synthetic scheme to be extendible to A-nor-steroids with the A:B-trans configuration.
The scope of the invention is defined in the following:
Claims (6)
1. A process for preparing A-nor and A-nor-18-homo-steroids of the formula:
wherein n=1 or 0, R is methyl or ethyl; R1 is hydrogen or
wherein A is lower alkyl, cyclo-alkyl or aryl; and R2 is hydrogen or methyl which comprises
(a) reacting an optically active trans-fused bicyclic diketo-sulfone of the formula::
with a 6-( 1 ,3-dioxolan-2-yl)-3-oxoheptanoic acid methyl ester or with a 5-( 1 ,3-dioxolan-2- yl)-3-nxohexanoic acid methyl ester to obtain a triketo derivative; (b) hydrolyzing, cyclizing and decarboxylating the product of step (a) to obtain an enone; (c) catalytically hydrogenating said enone to obtain a dione; (d) acid hydrolyzing to obtain a trione; (e) cyclizing the product of step (d) to obtain a mixture of isomeric enones; (f) subjecting said mixture to Birch reduction and oxidation to obtain the corresponding saturated 2,1 7-dione with the A:B trans stereochemistry; (g) ethynylating the product of step (f) to obtain a mixture of 2a- and 2p-isomers; and (h) separating the isomers by chromatography.
2. A process for preparing A-nor and A-nor-18-homo-steroids of the formula:
wherein n=1 or O, R is methyl or ethyl; R1 is hydrogen and R2 is hydrogen or methyl comprising
(a) reacting an optically active trans-fused bicyclic diketo-sulfone of the formula::
with a 6-(1,3-dioxolan-2-yl)-3-oxoheptanoic acid methyl ester or with a 5-(1,3-dioxolan-Z- yl)-3-oxohexanoic acid methyl ester to obtain a triketo derivative; (b) hydrolyzing, cyclizing and decarboxylating the product or step (a) to obtain an enone; (c) catalytically hydrogenating said enone to obtain a dione; (d) acid hydrolyzing to obtain a trione; (e) cyclizing the product of step (d) to obtain a mixture of isomeric enones; (f) subjecting said mixture to Birch reduction and oxidation to obtain the corresponding saturated
2,17-dione with the A:B trans stereochemistry; (g) ethynylating the product of step (f) to obtain a mixture of 2a- and 2-isomern; and (h) separating the isomers by chromatography.
3. A process for preparing A-nor and A-nor-18-homo-steroids of the formula:
wherein n =1 or 0, R is methyl or ethyl; R1 is
wherein A is lower alkyl, cyclo-alkyl or aryl; and R2 is hydrogen or methyl comprising esterifying the 2 isomer product made by the process of claim 2.
4. A process for preparing A-nor and A-nor-I 8-homo-steroids of the formula:
wherein n=1 or 0, R is methyl or ethyl; R1 is lower alkyl, cyclo-alkyl or aryl; and R2 is hydrogen or methyl comprising esterifying the 2a isomer product made by the process of claim 2.
5. A-nor and A-nor-1 8-homo-steroids having the formula:
wherein n=1 or 0, R is methyl or ethyl; R1 is hydrogen or A or
wherein A is lower alkyl, cyclo-alkyl or aryl; and R2 is hydrogen or methyl when prepared by the process of any of claims 1 1.
6. A process for preparing A-nor and A-nor-18-homo-steroids substantially as hereinbefore described.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR7920926A FR2465748A1 (en) | 1979-08-14 | 1979-08-14 | A-NOR-, A-NOR-18-HOMO-STEROIDS AND PROCESS FOR THEIR PREPARATION |
| US06/140,598 US4309565A (en) | 1979-08-14 | 1980-04-15 | Process for synthesizing A-nor and A-nor-18-homo-steroids |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| GB2061278A true GB2061278A (en) | 1981-05-13 |
| GB2061278B GB2061278B (en) | 1984-01-11 |
Family
ID=26221320
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB8026582A Expired GB2061278B (en) | 1979-08-14 | 1980-08-14 | Total synthesis of a-nor and a-dinor steroids |
Country Status (3)
| Country | Link |
|---|---|
| US (1) | US4309565A (en) |
| DE (1) | DE3028671A1 (en) |
| GB (1) | GB2061278B (en) |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3141025A (en) * | 1961-08-18 | 1964-07-14 | Roussel Uclaf | 17alpha-ethynyl-10beta-propyl-delta4, 9(11)-estradiene-17beta-ol-3-one and its preparation |
| US3803218A (en) * | 1964-09-29 | 1974-04-09 | Hoffmann La Roche | 11-substituted-desa-androstanes |
| US3816459A (en) * | 1964-09-29 | 1974-06-11 | Hoffmann La Roche | Substituted-desa-pregnanes and desa-pregnenes |
| US3772366A (en) * | 1964-09-29 | 1973-11-13 | Hoffmann La Roche | Process for the preparation of 9beta,10beta steroids |
| US4201869A (en) * | 1970-12-21 | 1980-05-06 | Hoffmann-La Roche Inc. | Intermediates for steroid total synthesis process utilizing asymmetric induction |
| US3932519A (en) * | 1970-12-21 | 1976-01-13 | Hoffmann-La Roche Inc. | 7,7A-Dihydro-4-[2-(3-alkoxyphenyl)-2-hydroxyethyl]-7a-alkyl-1, 5(6H)-indandiones,3,4,8,8a-tetrahydro-5-[2-(3-alkoxyphenyl)-2-hydroxyethyl]-8a-alkyl-1,6(7H)-naphthalenediones and processes for the preparation thereof utilizing asymmetric induction |
| US4011211A (en) * | 1973-10-16 | 1977-03-08 | Hoffmann-La Roche Inc. | Steroid total synthesis process utilizing asymmetric induction |
-
1980
- 1980-04-15 US US06/140,598 patent/US4309565A/en not_active Expired - Lifetime
- 1980-07-29 DE DE19803028671 patent/DE3028671A1/en not_active Withdrawn
- 1980-08-14 GB GB8026582A patent/GB2061278B/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| US4309565A (en) | 1982-01-05 |
| DE3028671A1 (en) | 1981-03-19 |
| GB2061278B (en) | 1984-01-11 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PCNP | Patent ceased through non-payment of renewal fee |